None.
(1) Field of the Invention
The present invention relates to deuterated therapeutic compounds for the treatment of psychiatric disorders. In particular, the present invention relates to the use of deuterated tryptophan, tryptamine, serotonin, melatonin, norepinephrine, vanilmandelic acid, vanitiolide, methionine, pyridoxine-5-phosphate, and derivatives therefrom as therapeutic agents.
(2) Description of Related Art
Deuterium oxide, otherwise known as heavy water, has been to shown to have a chronomutagenic effect on the period and entrainment of the light-dark (LD) cycle of mice (Hayes and Palmer, Int. J. Chromobiol 4:63-69 (1976); and, Biol. Bull 143 513-524 (1972)). In particular, it has been shown that deuterium oxide suppressed the spontaneous locomotor activity of the mouse (Hayes and Palmer, Experientia, 4: 469-470 (1976)) Other references are Rutger Wever, In The Circadian System of Man, Springer Verlag; and, Mohammud and Sharon Shaffi, In Phototherapy, Biological Rhythms, Mood Disorders, and the Pineal Gland, American Psychiatric Press (1990). These cycles are also related to the manic depressive state in humans.
Lithium compounds are used for the treatment of manic depressive disorders; however, the lithium compounds are quite dosage sensitive and can be toxic to the patient at high dosages. Thus, it would be desirable to provide compounds for the treatment of these psychiatric disorders which are less dosage sensitive and toxic than lithium-based compounds.
Deuterated compounds and compositions for use in pharmaceutical applications has been the object several patents. These patents have shown that particular deuterated compounds or compositions have enhanced stability or enhanced efficacy at lower dosage levels.
U.S. Pat. No. 4,473,585 to Abrahamsson et al discloses deuterated acids, in particular perdeuterated N-hendecanoic acid or 2,2-dideutero-N-hendecanoic acid, and their use for protecting an object against attack by destructive fungi. The patent indicates that short chain compounds (citric acid) may have an undesired affect on humans.
U.S. Pat. No. 5,223,269 to Liepins discloses methods and deuterium containing compositions for treating hypertension. In particular, the compositions that are disclosed contain deuterium oxide, deuterated foods, or deuterated antihypertensive drugs.
U.S. Pat. No. 5,846,514 to Foster et al discloses a method for enhancing drug efficiency and duration of action by using drugs wherein one or more hydrogen atoms of the drug are deuterated. In particular, the method produces deuterated compounds such as nifedipine, a drug for treatment of hypertension, and penicillins.
U.S. Pat. No. 5,858,375 to Furminger et al discloses pharmaceutical compositions that consist of the drug in deuterium oxide wherein the deuterium oxide enhances the stability of the composition. In particular, the compositions relate to virus vaccines in a stabilizer consisting of deuterium oxide and other stabilizers.
U.S. Pat. No. 5,895,660 to Hoffmann et al discloses a method for enhancing the adsorption of drugs in transdermal application wherein a deuterated analogue of the drug is applied-the skin.
The present invention provides a method for treating psychiatric disorders, in particular, depression, by providing deuterated compounds to a human or animal patient. The deuterated compounds are deuterated derivatives of compounds that target the pineal gland and include such compounds as tranquilizers, basic metabolites, enzyme cofactors, specific precursors of pineal neurohormones, or neurohormonal intermediates. The deuterated compounds can be administered orally, intranasally, intravenously, or by inoculation. The preferred method is oral administration.
Therefore, the present invention provides a method of treating a depressive symptom in a human patient which comprises administering an assimilable organic deuterium compound to the patient in an amount which reduces the depressive symptoms of the patient. In particular, the patient is a manic depressive.
Further, the present invention provides a method for effecting a mental change in a human which comprises administering an effective amount of 2-hydroxy-1,2,3-trideuteropropane tricarboxylic acid which has the formula
CH2(COOD)CH(COOD)CH2(COOD)
wherein D is a deuterium atom to the human to thereby effect the mental change in the human patient. In particular, wherein the patient is manic is depressive.
Further still, the present invention provides a method for chemically changing a biological clock of a human which comprises administering an effective amount of a non-toxic deuterated organic compound to the patient so that the biological clock is changed. This method is particularly useful when the patient is a manic depressive.
The method of the present invention further provides for one or more deuterated compounds which are selected from the group consisting of deuterated tryptophan, deuterated 5-hydroxytryptophan, deuterated serotonin, deuterated N-acetyl serotonin, deuterated melatonin, deuterated citrate, deuterated pyridoxin-5-phosphate, deuterated methionine, deuterated vanitiolide, deuterated vanilmandelic acid, deuterated norepinephrine, and deuterated derivatives thereof.
In a preferred embodiment, the deuterated tryptophan compound has the formula 
wherein R is a protium atom or deuterium atom and at least one R is a deuterium atom.
In a preferred embodiment, the deuterated 5-hydroxytryptophan compound has the formula 
wherein R is a proton or deuterium atom and at least one R is a deuterium atom.
In a preferred embodiment, the deuterated serotonin compound has the formula 
wherein R is a proton or deuterium atom and at least one R is a deuterium atom.
In a preferred embodiment, the deuterated N-acetyl serotonin compound has the formula 
wherein R is a proton or deuterium atom and at least one R is a deuterium atom.
In a preferred embodiment, the deuterated melatonin compound has the formula 
wherein R is a proton or deuterium atom and at least one R is a deuterium atom.
In a preferred embodiment, the deuterated pyridoxin-5-phosphate compound has the formula 
wherein R is a proton or deuterium atom and at least one R is a deuterium atom.
In a preferred embodiment, the deuterated methionine compound has the formula
CR3SCR2CR2CR(NR2)COOR
wherein R is a proton or deuterium atom and at least one R is a deuterium atom.
In a preferred embodiment, the deuterated vanitiolide compound has the formula 
wherein R is a proton or deuterium atom and at least one R is a deuterium atom.
In a preferred embodiment, the deuterated norepinephrine compound has the formula 
wherein R is a proton or deuterium atom and at least one R is a deuterium atom.
In a preferred embodiment, the deuterated vanilmandelic compound has the formula 
wherein R is a proton or deuterium atom and at least one R is a deuterium atom.
Methods for preparing the deuterated compounds of the present invention are also provided.
Therefore, it is an objective of the present invention to provide a method for the treatment of psychiatric disorders by administering deuterated compounds to the animal or human patient.
It is also an object of the present invention to provide compositions for the treatment of psychiatric disorders that are safer than current compounds which are used for treating psychiatric disorders.